The Crowdsourced Replication Initiative: Investigating Immigration and Social Policy Preferences. Executive Report.

In an era of mass migration, social scientists, populist parties and social movements raise concerns over the future of immigration-destination societies. What impacts does this have on policy and social solidarity? Comparative cross-national research, relying mostly on secondary data, has findings in different directions. There is a threat of selective model reporting and lack of replicability. The heterogeneity of countries obscures attempts to clearly define data-generating models. P-hacking and HARKing lurk among standard research practices in this area.This project employs crowdsourcing to address these issues. It draws on replication, deliberation, meta-analysis and harnessing the power of many minds at once. The Crowdsourced Replication Initiative carries two main goals, (a) to better investigate the linkage between immigration and social policy preferences across countries, and (b) to develop crowdsourcing as a social science method. The Executive Report provides short reviews of the area of social policy preferences and immigration, and the methods and impetus behind crowdsourcing plus a description of the entire project. Three main areas of findings will appear in three papers, that are registered as PAPs or in process

Anti-inflammatory consequences of bile acid accumulation in virus-infected bile duct ligated mice.

Cholestatic patients exhibiting high bile acid serum levels were reported to be more susceptible to bacterial and viral infections. Animal studies in bile duct ligated (BDL) mice suggest that cholestasis leads to an aggravation of hepatic bacterial infections. We have investigated the impact of cholestasis on mouse cytomegalovirus (MCMV)-induced immune responses and viral replication. While MCMV did not aggravate BDL-induced liver damage, BDL markedly reduced MCMV-triggered chemokine expression and immune cell recruitment to the liver. MCMV-infected BDL mice showed diminished trafficking of Ly6C+/F4/80+ myeloid cells and NK1.1+ NK cells to the liver compared to MCMV infected control mice. Moreover, virus-driven expression of CCL7, CCL12, CXCL9 and CXCL10 was clearly impaired in BDL- compared to sham-operated mice. Furthermore, production of the anti-inflammatory cytokine IL-10 was massively augmented in infected BDL mice. In contrast, intra- and extrahepatic virus replication was unaltered in BDL-MCMV mice when compared to sham-MCMV mice. Cholestasis in the BDL model severely impaired pathogen-induced chemokine expression in the liver affecting CCR2- and CXCR3-dependent cell trafficking. Cholestasis resulted in reduced recruitment of inflammatory monocytes and NK cells to the liver

BDL leads to increased bile acid concentrations in blood plasma.

<p>BDL leads to increased bile acid concentrations in blood plasma.</p

BDL diminishes MCMV-induced chemokine induction.

<p>Sham or BDL operated mice were either mock treated or infected with MCMV-luc (2x10⁵ PFU/ml) and 72 hpi organs were harvested. Total RNA of liver tissue was prepared and chemokine mRNA expression was analyzed by qPCR using specific primers or TaqMan primers and probes. Relative gene expression was calculated by the ΔΔCt method using ActB or SDHA as housekeeping gene. Depicted are the mean values ± SEM of (A) <i>Cxcl2</i>, (B) <i>Ccl2</i>, (C) <i>Ccl12</i>, (D) <i>Ccl7</i>, (E) <i>Ccl4</i> and (F) <i>Cxcl10</i> from the indicated groups of mice (sham n = 5; BDL n = 4; sham-MCMV n = 9; BDL-MCMV n = 9). Statistical significance was calculated with Mann-Whitney-U-tests (***p< 0.001, **p< 0.01, *p< 0.05, ns: not significant).</p

BDL modifies plasma chemokine and cytokine levels.

<p>Blood of sham- or BDL-operated animals that were either mock or MCMV-luc (2x10⁵ PFU/ml) infected was collected 24 and 72 hpi. Plasma protein levels of (A) CCL7, (B) CXCL10 or (C) IL-10 were measured using a magnetic screening assay. Depicted are the mean values ± SEM from the indicated mouse groups (24 hpi: sham n = 8; BDL n = 10; sham-MCMV n = 10; BDL-MCMV n = 10; 72 hpi: sham n = 5; BDL n = 4; sham-MCMV n = 9; BDL-MCMV n = 9). Statistical significance was calculated with Mann-Whitney-U-tests (***p< 0.001, **p< 0.01, *p< 0.05, ns: not significant).</p

BDL alters the immune cell profile of MCMVinfected livers.

<p>Sham- or BDL-operated mice were either mock treated or infected with MCMV-luc (2x10⁵ PFU/ml) and 72 hpi organs were harvested. Total RNA of liver tissue was prepared and cell marker mRNA expression was analyzed by qPCR using specific TaqMan primers and probes. Relative gene expression was calculated by the ΔΔCt method using RPII or SDHA as housekeeping gene. Depicted are the mean values ± SEM of (A) PLZF, (B) CD11b, (C) Ly6C, (D) F4/80, (E) NK1.1 and (F) CD335 from the indicated groups of mice (sham n = 5; BDL n = 4; sham MCMV n = 9; BDL MCMV n = 9). Statistical significance was calculated with Mann-Whitney-U-tests (***p< 0.001, **p< 0.01, *p< 0.05, ns: not significant).</p

BDL is not associated with diminished MCMV replication.

<p>Sham or BDL operated mice were infected with MCMV-luc (2x10⁵ PFU/ml) and 72 hpi organs were harvested. Total RNA of liver or spleen tissue was prepared and MCMV <i>ie3</i> mRNA expression was analyzed by qPCR using specific primers or TaqMan primers and probes. Relative gene expression was calculated by the ΔΔCt method using RPII or SDHA as housekeeping gene. Depicted are the mean values ± SEM of (A) liver tissue and (B) spleen tissue 72 hpi from the indicated groups of mice (sham-MCMV n = 9; BDL-MCMV n = 9). Statistical significance was calculated with Mann-Whitney-U-tests. Organ homogenates of (C) livers or (D) spleens were generated 72 hpi and virus-tissue suspensions were titrated on murine fibroblasts. 24 h post titration luciferase activity was measured and virus titers were calculated using a standard curve. Each square represents one sample, the black line illustrates the median of each group and the dotted line displays the detection limit. Statistical significance was calculated with Mann-Whitney-U-tests (ns: not significant).</p

Pooled RT-qPCR testing for SARS-CoV-2 surveillance in schools - a cluster randomised trial

Background: The extent to which children and adolescents contribute to SARS-CoV-2 transmission remains not fully understood. Novel high-capacity testing methods may provide real-time epidemiological data in educational settings helping to establish a rational approach to prevent and minimize SARS-CoV-2 transmission. We investigated whether pooling of samples for SARS-CoV-2 detection by RT-qPCR is a sensitive and feasible high-capacity diagnostic strategy for surveillance of SARS-CoV-2 infections in schools. Methods: In this study, students and school staff of 14 educational facilities in Germany were tested sequentially between November 9 and December 23, 2020, two or three times per week for at least three consecutive weeks. Participants were randomized for evaluation of two different age adjusted swab sampling methods (oropharyngeal swabs or buccal swabs compared to saliva swabs using a ‘lolli method’). Swabs were collected and pooled for SARS-CoV-2 RT-qPCR. Individuals of positive pooled tests were retested by RT-qPCR the same or the following day. Positive individuals were quarantined while the SARS-CoV-2 negative individuals remained in class with continued pooled RT-qPCR surveillance. The study is registered with the German Clinical Trials register (registration number: DRKS00023911). Findings: 5,537 individuals were eligible and 3970 participants were enroled and included in the analysis. In students, a total of 21,978 swabs were taken and combined in 2218 pooled RT-qPCR tests. We detected 41 positive pooled tests (1·8%) leading to 36 SARS-CoV-2 cases among students which could be identified by individual re-testing. The cumulative 3-week incidence for primary schools was 564/100,000 (6/1064, additionally 1 infection detected in week 4) and 1249/100,000 (29/2322) for secondary schools. In secondary schools, there was no difference in the number of SARS-CoV-2 positive students identified from pooled oropharyngeal swabs compared to those identified from pooled saliva samples (lolli method) (14 vs. 15 cases; 1·3% vs. 1·3%; OR 1.1; 95%-CI 0·5–2·5). A single secondary school accounted for 17 of 36 cases (47%) indicating a high burden of asymptomatic prevalent SARS-CoV-2 cases in the respective school and community. Interpretation: In educational settings, SARS-CoV-2 screening by RT-qPCR-based pooled testing with easily obtainable saliva samples is a feasible method to detect incident cases and observe transmission dynamics. Funding: Federal Ministry of education and research (BMBF; Project B-FAST in “NaFoUniMedCovid19”; registration number: 01KX2021)

The Crowdsourced Replication Initiative: Investigating Immigration and Social Policy Preferences. Executive Report

Breznau N, Rinke EM, Wuttke A, et al. The Crowdsourced Replication Initiative: Investigating Immigration and Social Policy Preferences. Executive Report. 2019